RESCUE THERAPY WITH TACROLIMUS AFTER COMBINED KIDNEY PANCREAS AND ISOLATED PANCREAS TRANSPLANTATION IN PATIENTS WITH SEVERE CYCLOSPORINE NEPHROTOXICITY/

This study details 11 pancreas transplant recipients (10 combined kidn ey and pancreas and 1 pancreas after kidney) who were converted to tac rolimus (FK506) due to acute severe cyclosporine nephrotoxicity in 8 c ases and persistent rejection with cyclosporine toxicity in three case s. Arteriolopathy was documented by renal histology in all cases. Cycl osporine was discontinued for 24 hr immediately prior to initiation of tacrolimus. Tacrolimus was started orally at 0.1 mg/kg twice daily wi th dose adjustments to maintain whole blood trough levels of 8-15 ng/m L by IMx, Tacrolimus was initiated a mean of 14.5 months (range 1-81) after pancreas transplantation. The mean serum creatinine level had in creased to 2.9 mg/dl from 1.0 mg/dl at the diagnosis of cyclosporine a rteriolopathy (P=0.003). The mean serum creatinine and blood glucose l evels at the time of initiation of tacrolimus were 2.1 mg/dl and 104 m g/dl, respectively. Serum creatinine was 1.7 mg/dl, 1.9 mg/dl, 1.8 mg/ dl, and 1.7 mg/dl after 1, 2, 3, and 6 months of tacrolimus therapy, r espectively; ANOVA (P=0.02). The corresponding blood glucose levels we re 117 mg/dl, 112 mg/dl, 109 mg/dl, and 116 mg/dl, respectively (P=NS) , Normal C-peptide levels were present before (5.9 ng/ml) and after (6 .2 ng/ml), the initiation of tacrolimus therapy (P=NS), and mean HbA(1 )C was 6.1% before and 6.3% after tacrolimus therapy, (P=NS), There we re 4 episodes of acute rejection, 3 responded to intravenous methylpre dnisolone, and 1 required OKT3 during tacrolimus therapy, Reversible t acrolimus nephrotoxicity was noted in three patients without any evide nce of progressive vasculopathy, All 11 patients are alive, and 10/11 kidney and pancreas grafts are functioning with a mean follow-up of 7. 7 months (range 5-10), In this study, conversion from cyclosporine to tacrolimus in kidney and pancreas recipients resulted in improvement a nd stabilization of renal function while maintaining stable blood gluc ose, C peptide, and HbA(1)C levels.